Thromboprophylaxis with Low Molecular Weight Heparin (Fragmin) in High Risk Pregnancies

Summary

Venous thromboembolic disease remains the commonest cause of maternal death. The management of thromboprophylaxis in high risk women during pregnancy is contentious. Low molecular weight heparins (LMW) have theoretical advantages compared with unfractionated heparin and warfarin but have been poorly studied in pregnancy. We report on the use of LMW heparin (Fragmin) as thromboprophylaxis in thirty four high risk pregnancies.

All the women had a previous thrombosis or a thrombosis in their current pregnancy +/- a recognised thrombophilic state (eleven had the antiphospholipid syndrome).

Fragmin was given subcutaneously to maintain trough anti-Xa activity of 0.15-0.2 U/ml and 2 h post injection levels of 0.4-0.6 U/ml. The levels were checked monthly during pregnancy. Most women required 5,000U Fragmin once daily during the first trimester unless they were greater than 100 kg at the start of pregnancy. The mean time for dosage increase was 20.5 week (S.D. 8.2). 26/34 pregnancies (76%) required twice daily at the end of pregnancy. Epidural anaesthesia was managed by omitting Fragmin dose or inserting the needle 6 hours after the previous Fragmin injection. There were no thromboembolic events, thrombocytopenias or excessive haemorrhage. One woman had osteoporotic vertebral collapse post partum, she had no other risk factors for osteoporosis.

LWM heparin (Fragmin) appears to be efficacious in preventing recurrent thromboembolic disease in pregnant women at high risk, but it is notable that osteoporotic fractures occurred post partum in one woman. Further trials are required to determine optimal dosage and safety.

• References

• 1 Turnball A, Tindall VR, Beard RW. Report on confidential enquires into maternal death in England and Wales 1982-1984. HMSO 1989; 28-36
• 2 Babaracco MA, Vessey M. Recurrence of venous thromboembolism and the use of the oral contraceptives. Br Med J 1974; 02: 215-217
• 3 Harris EN. Syndrome of the black swan. Br J Rheumatol 1989; 26: 324-326
• 4 Forestier F, Daffos F, Rainaut M, Toulemonde F. Low molecular weight heparin (CY216) does not cross the placenta during the third trimester of pregnancy. Thromb Haemost 1987; 57: 234
• 5 Melissari E, Parker CJ, Kakkar VV. Use of low molecular weight heparin in pregnancy. Thromb Haemost 1989; 62: 451-453
• 6 Harenberg J, Schneider D, Heilman L, Wolf H. Lack of anti-Xa activity in umbilical cord vein samples after subcutaneous administration of heparin or low molecular mass heparin in pregnant women. Haemostasis 1993; 23: 314-320
• 7 Ginsberg JS, Hirsh J. Anticoagulants during pregnancy. Ann Rev Med 1989; 40: 79-86
• 8 Ginsberg JS, Kowalchuk G, Hirsh J, Brill-Edwards P, Burrows R, Coates G, Webber C. Heparin effects on bone density. Thromb Haemost 1990; 64: 286-289
• 9 Gillis S, Shushan A, Eldor A. Use of low molecular weight heparin for prophylaxis and treatment of thromboembolism in pregnancy. Int J Gynaecol Obstet 1992; 39: 297-301
• 10 Melissari E, Parker CJ, Wilson NV, Monti G, Kanthon C, Pemberton KD, Nicolaides KH, Barrett JJ, Kakkar VV. Use of low molecular weight heparin in pregnancy. Thromb Haemost 1992; 68: 652-656
• 11 Sturridge F, de SwietM, Letsky E. The use of low molecular weight heparin for thromboprophylaxis in pregnancy. Br J Obstet Gynaecol 1994; 101: 699-771
• 12 Kurineczuk J. Pulmonary embolus and maternal mortality in the antenatal period – evidence of a trend. Health Trends 1993; 25: 23-25
• 13 Conard J, Horellen MH, Van Dreden P, Lecompte T, Samama M. Thrombosis and pregnancy in congenital deficiencies in antithrombin III, protein C or protein S: Study of 78 women. Thromb Haemost 1990; 63: 319-320
• 14 Lima F, Khamashta MA, Buchanan NM, Kerslake S, Hunt BJ, Hughes GRV. A study of 60 pregnancies in patients with the antiphospholipid syndrome. Clin Exp Rheumatol 1996; 14: 131-136
• 15 The British Society for Haematology. Guidelines on the prevention, investigation and management of thrombosis associated with pregnancy. J Clin Pathol 1993; 46: 489-496
• 16 Khamashta MA, Cuadrado MJ, Mujic F, Taub N, Hunt BJ, Hughes GRV. The antithrombotic management of the antiphospholipid syndrome. New Eng J Med 1995; 332: 993-997
• 17 Buchanan NMM, Khamashta MA, Morton KE, Kerslake S, Baguley EA, Hughes GRV. A study of 100 high risk lupus pregnancies. Am J Reprod Immunol 1992; 28: 192-194
• 18 Dahlman TC. Osteoporotic fractures and the recurrence of thromboembolism during pregnancy and the puerperium in 184 women undergoing thromboprophylaxis with heparin. Am J Obstet Gynaecol 1993; 168: 1265-1270
• 19 Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992; 79: 1-17
• 20 Shefras J, Farquharson R. Bone density changes in pregnant women receiving heparin. Eur J Obst Gynaecol Repro Biol 1996; 65: 171-174
• 21 Rao TLK, El-Etr AA. Anticoagulation following placement of epidurals and subarachnoid catheters: an evaluation of neurological sequelae. Anaesthesiology 1981; 55: 618-620
• 22 Will-Jorgensen P, Jorgenson N, Rasmussen LS. Lumbar regional anaesthesia and prophylactic anticoagulant therapy: is the combination safe?. Anaesthesia 1991; 46: 623-627
• 23 Wildsmith JAW, McClure JH. Anticoagulant drugs and central nerve blockade. Anaesthesia 1991; 46: 613-614
• 24 Boda Z, Laszlo P, Rejto I, Tomai I, Pfliegler G, Blasko G, Rak K. Low molecular weight heparin as thromboprophylaxis in familial thrombophilia during the whole period of pregnancy. Thromb Haemost 1996; 76: 124-128